A 3-month-old infant presents with bilateral absence of the iris noted on routine neonatal screening. On examination, the child has nystagmus, photophobia, and foveal hypoplasia. The pediatrician suspects the chromosomal abnormality marked **A** in the diagram. Which of the following best describes the genetic basis and primary clinical consequence of this deletion?

Question

Accepted Answer

D. Interstitial deletion of 11p13 encompassing WT1 and PAX6 genes, causing aniridia as the first detectable feature and conferring ~50% lifetime risk of Wilms tumor. ## Why option 1 is right

The structure marked **A** represents the 11p13 deletion characteristic of WAGR syndrome. This contiguous gene deletion encompasses both WT1 (Wilms tumor 1) and PAX6 (paired box gene 6) tumor-suppressor genes. PAX6 haploinsufficiency causes congenital aniridia (bilateral absence of iris), which is the **first detectable feature at birth**, accompanied by foveal hypoplasia, nystagmus, and photophobia—exactly as presented in this infant. WT1 haploinsufficiency confers a ~50% lifetime risk of Wilms tumor, typically presenting at ages 2–3 years, often bilateral. This is the cardinal feature set summarized by the WAGR acronym (Wilms tumor, Aniridia, Genitourinary anomalies, intellectual disability/Retardation). Per Nelson Pediatrics 22e, Ch 543, any infant with sporadic aniridia must be evaluated for 11p13 deletion since 30–50% have WAGR.

## Why each distractor is wrong

- **Option 2**: Describes 11p15.5 deletion (Beckwith-Wiedemann syndrome), which presents with macroglossia, exomphalos, and organomegaly—not aniridia. This is marked **B** in the diagram, not **A**.
- **Option 3**: Describes 13q14 monosomy (retinoblastoma), which presents with intraocular tumor typically diagnosed after age 5 years, not congenital aniridia with nystagmus and foveal hypoplasia. This is marked **C**, not **A**.
- **Option 4**: Describes 17p13 deletion (Smith-Magenis syndrome), which presents with growth retardation, developmental delay, and behavioral problems—not ocular features like aniridia. This is marked **D**, not **A**.

**High-Yield:** Sporadic aniridia = WAGR until proven otherwise; 30–50% of sporadic aniridia cases harbor 11p13 deletion; PAX6 loss causes the eye findings, WT1 loss causes Wilms tumor and GU anomalies.

[cite: Nelson Pediatrics 22e, Ch 543]

Answer

A. Monosomy of 13q14 with RB1 gene loss, manifesting as unilateral retinoblastoma typically diagnosed after age 5 years

Answer

B. Interstitial deletion of 17p13 affecting TP53, presenting with growth retardation and developmental delay without ocular involvement

Answer

C. Interstitial deletion of 11p15.5 affecting IGF2 and H19, presenting with macroglossia and exomphalos in the neonatal period

Explanation

Why option 1 is right

Why each distractor is wrong

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